Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of Sorafenib and Eribulin in Combination
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Purpose
This Phase 1 study will be conducted in an open-label, non-randomized, dose-escalation design in subjects with advanced, metastatic or refractory solid malignancy who are not candidates for standard therapy. The study drugs are sorafenib and eribulin mesylate.
Up to 24 subjects with solid tumors will participate in the dose escalation part of the study, and once the maximum tolerated dose is defined, 24-30 subjects with metastatic breast cancer will participate in the expansion phase of the study.
Eribulin (mesylate) will be administered intravenously at a fixed dose of 1.4 mg/m2 on Days 1 and 8 of 21-day Cycles.
The starting sorafenib dose (Dose Level 1) is 200 mg twice daily. Sorafenib is given orally, continuously on days 11 to 21 of Cycle 1, and from Day 1 to Day 21 of all subsequent cycles. If 200 mg sorafenib twice daily is tolerated with eribulin, the sorafenib dose will be escalated sequentially to 200 mg morning dose and 400 mg evening dose (Dose Level 2) in a new cohort. If Dose Level 2 is tolerated, a second dose escalation to 400 mg twice daily (Dose Level 3) will be studied in a new cohort. If the starting dose of sorafenib is not tolerated with eribulin, the sorafenib dose will be de-escalated to 200 mg once daily in a new cohort.
Subjects will need to receive two cycles of eribulin plus sorafenib therapy and safety data for the first and second cycle needs to be available before the start of the next cohort.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Neoplasms |
Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Eribulin |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1, Multi-center, Non-randomized, Open Label, Dose Escalation Design Study of Sorafenib (BAY43-9006) in Combination With Eribulin in Subjects With Advanced, Metastatic or Refractory Solid Tumors |
- Number of participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 30 months ] [ Designated as safety issue: Yes ]
- AUC (area under the plasma concentration vs time curve) of BAY43-9006 [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
- Cmax (maximum drug concentration in plasma after single dose administration) of BAY43-9006 [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: No ]
- QT time, assessed by QTcF / QTcB (QT interval corrected for heart rate according to Fridericia / Bazett) [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: Yes ]
- Clinical benefit and response measured by RESIST (1.1) criteria [ Time Frame: Approximately 3-18 weeks depending on tumor response ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 54 |
| Study Start Date: | July 2012 |
| Estimated Study Completion Date: | July 2014 |
| Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Arm 1 |
Drug: Sorafenib (Nexavar, BAY43-9006)
Sorafenib (starting dose of 200 mg bid, level 1) administration will begin on Day 11 of Cycle 1, and will be administered twice daily continuously. If the combination is well tolerated, the dose will be escalated in new cohorts to 200 mg AM and 400 mg PM (level 2), then subsequently to 400 mg bid (level 3). If sorafenib starting dose (level 1) is not well tolerated with eribulin, the sorafenib dose will be de-escalated to 200 mg qd (Dose Level -1) in a new cohort. Eribulin: 1.4 mg/m2 as an intravenous infusion on Days 1 and 8 of each 21-day cycle.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Study population:
- For dose escalation cohorts: Subjects with advanced, metastatic or refractory solid malignancy who are not candidates for standard therapy
- For expansion cohort only: Histologically or cytologically proven metastatic breast cancer that is refractory to standard therapy and not amenable to surgery with curative intent. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Male or female at least 18 years of age
- Predicted life expectancy of at least 12 weeks
- Able to swallow and retain oral medication
Exclusion Criteria:
- Prolonged corrected QT (QTc), defined as QTcF (QT interval corrected for heart rate according to Fridericia) interval > 450 msec at screening by central reader
- Cardiac disease: Congestive heart failure > NYHA Class II; subjects must not have unstable angina (angina symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Arterial or venous thrombi, including cerebrovascular accident and myocardial infarction in the past 6 months
- Pulmonary hemorrhage event ≥ CTCAE (common toxicity criteria for adverse events) Grade 2 within 4 weeks
- Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks
- Chemotherapy, hormonal therapy, investigational drugs, or radiotherapy within the last 28 days and/or not recovered (< Grade 1) from prior therapy. Start of study treatment is allowed within less than 28 days of the prior therapy provided that 5 half-lives of the prior treatment drug(s) have elapsed.
- Use of medication that may prolong QTc
Contacts and Locations| Contact: Bayer Clinical Trials Contact | clinical-trials-contact@bayerhealthcare.com |
| France | |
| Recruiting | |
| Toulouse, France, 31052 | |
| Germany | |
| Recruiting | |
| Freiburg, Baden-Württemberg, Germany, 79106 | |
| Recruiting | |
| Heidelberg, Baden-Württemberg, Germany, 69120 | |
| Study Director: | Bayer Study Director | Bayer |
More Information
Additional Information:
No publications provided
| Responsible Party: | Head of Clinical Sciences, Bayer Healthcare AG |
| ClinicalTrials.gov Identifier: | NCT01585870 History of Changes |
| Other Study ID Numbers: | 15977, 2011-005849-12 |
| Study First Received: | April 12, 2012 |
| Last Updated: | May 3, 2013 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Bayer:
|
Safety Tolerability Pharmacokinetics Clinical benefit |
Sorafenib Eribulin Breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Sorafenib |
Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 21, 2013